Researchers Rejuvenate Dormant Stem Cells in Aging Brains

Scientists in Luxembourg have been able to rejuvenate stem cells in the brains of aging mice and have improved the regeneration of neurons in injured parts of the brain.

Stem cells have the potential to be used in regenerative medicine to help the body heal faster. Stem cells have the ability to turn into any cell type and form all of the cells in the body. Over time however, the body’s ability to heal itself diminishes.

In certain areas of the adult brain, stem cells remain functional for life and can develop new nerve cells following injury, but their ability to replenish neurons diminishes over time. Stem cell numbers fall and those that remain go into a state of dormancy. If those dormant stem cells could be awoken, repair processes could be triggered.

Researchers at the University of Luxembourg’s Luxembourg Centre for Systems Biomedicine (LCSB) and the German Cancer Research Center (DKFZ) have been investigating how to reactivate stem cells that have become dormant.

The researchers demonstrated that as mice age, the number of stem cells in their brains decreases and those that are present are in a state of dormancy.

As stem cells differentiate into nerve cells, the concentration reduces as only a small percentage of stem cells form new stem cells. “If they did not increasingly enter into a state of dormancy without dividing actively as the brain ages, the supply of stem cells in the brain of an old mouse would be completely exhausted. They are using the dormancy to gain time,” explained the researchers.

Awakening stem cells is a challenge. Even in response to emergency signals from an injury, the stem cells are difficult to awaken. But if that process could be triggered, stem cells could be stimulated to repair injured brain tissue.

“Stem cells live in a niche where they constantly interact with other cells and extra-cellular components. It is extremely difficult to model such a plethora of complex molecular interactions on the computer,” explained Prof. Antonio del Sol of the LCSB. “We stopped thinking about what external factors were affecting the stem cells and started thinking about what the internal state of a stem cell would be like in its precisely defined niche.”

Through their research, the team discovered that stem cell dormancy was promoted by an inflammatory chemical messenger protein (sFRP5) in the Wnt signaling chain in the immediate environment of the stem cells. The researchers found that by introducing antibodies that block those signals, the dividing ability of neuronal stem cells increased, and stem cells started to proliferate. Reawakened stems cells were also shown to be as potent as stem cells in younger mice.

“With the deactivation of sFRP5, the cells undergo a kind of rejuvenation,” del Sol explained: “As a result, the ratio of active to dormant stem cells in the brain of old mice becomes almost as favorable as in young animals.”

Since it is possible to use drugs to reduce inflammation, they could potentially be used to reinvigorate dormant stem cells which would then initiate the repair of damaged neurons in old age.

The researchers’ findings are detailed in the paper – Quiescence modulates stem cell maintenance 1 and regenerative capacity in the aging brain – which was recently published in the journal Cell. DOI: 10.1016/j.cell.2019.01.040